1. Field of the Invention
The present invention relates generally to the fields of endocrinology, protein chemistry and biomedical engineering. More specifically, the present invention relates to a novel encapsulation system for the immunoisolation of living cells.
2. Description of the Related Art
Transplantation of cells to treat a variety of human diseases, such as diseases caused by hormone or protein deficiencies, is limited because transplanted cells are destroyed quickly by the recipient's immune system. To overcome this limitation, it is desirable that hormone- or protein-secreting cells be enclosed in a semi-permeable membrane that would protect cells from immune attack, while allowing the influx of molecules important for cell function/survival and efflux of the desired cellular products (see refs. 1-7).
The principle of immunoisolation or immunoprotection of cells for transplantation overcomes two main obstacles: 1) cell transplantation without the need for immunosuppression and its accompanying side effects, and 2) transplantation of cells from non-human species (xenograft) to overcome the limited supply of donor cells for such diseases as diabetes (refs. 8-12). Many diseases may be treated best by the regulated release of a cellular product (hormone, protein, neurotransmitter, etc.). Thus, a variety of cell types are candidates for transplantation of immunoisolated cells, including pancreatic islets, hepatocytes, neurons, parathyroid cells, and cells secreting various clotting factors.
One immunoisolation approach, encapsulation of pancreatic islets, is under investigation by a large number of groups and has been successful in reversing chemically-induced diabetes in rodents and in a small scale human clinical trial (refs. 1-3, 6, 13-17). Most cell encapsulation currently utilizes modifications of the procedure originated by Lim and Sun in which the encapsulant is suspended in a polyanionic aqueous solution and extruded by an air jet/syringe pump droplet generator into calcium ions (refs. 18 and 19). Poly(L-lysine), which is a cationic macromolecule, is then mixed with the hardened polyanionic gel, and a membrane is formed at the interface as a result of the ionic interaction. Because this is a binary system, however, all membrane parameters are tied to a single chemical complex. Attempts to optimize one parameter will affect all other parameters. The inability to adjust capsule parameters independently (for example, mechanical strength or permeability) has limited the success of this system (refs. 13 and 20). Capsules made with other binary polymer systems, such as Hydroxyethyl methacrylate/Methyl methacrylate (HEMA/MMA) suffer similar limitations (refs. 19, 21 and 22).
The prior art is deficient in the lack of effective means of encapsulating and immunoisolating living cells. The present invention fulfills this long-standing need and desire in the art.